Our work was concerned with the causes and prevention of cholesterol gallstones. The relationship between obesity and gallstone formation was examined by determining effects of obesity of saturation of gallbladder bile, hepatic secretion rates of biliary lipids, and pool sizes of bile acids. It was found that obese patients have a highly supersaturated gallbladder bile, and this abnormality is due to increased hepatic secretion of cholesterol. The increase in saturation was not due to a decrease in bile acid pool sizes such as previously reported for non-obese gallstone patients. Thus, we have shown that supersaturated or "lithogenic" bile occurs by a different mechanism than that of non-obese patients with stones. Also, caloric restriction in those patients was not associated with a decrease in bile lithogenicity, and during a period of active weight loss obese patents may actually be at increased risk for gallstone formation; however, after reestablishment of weight at a lower level lithogenicity is found to be definitely decreased. In addition, studies on hyperlipidemic patients treated with lipid lowering agents (polyunsaturated fats, clofibrate, and anion exchange resins) showed that lithogenicity of bile is frequently increased and thus treatment of hyperlipidemia may carry some greater risk of gallstones.